Glycosides of 2-alkyl-1, 4-naphthohydroquinone



ticular towate Patented D c. "14,1943

UNITED f ems-she. smiuill mistfqu; n1..-

assilnors" tul-v stim li-c eases No h m- Tet-2. 1. zeom 'i V The pre ent inventionis directed to 01. fl-alkyl-lA-naphthohydroquihoneiand inparr soluble lantihen orrhag'lc substances i 1 3 The compounds or 'thejpresentginvehtlon may m h ires iia" 1,1 Le r a su methyl, ethyl, propyl; butyl; etc and both R's.

represent like or 'slycoside'groups, such-as- I sure.

sulting. barium hydrozdde-ireesolution evapor'ated around 359-40 C.,,under-reduced pres-' Thesolid residue containing lunwanted bariumacetate as well as the tree glucosideuis then extracted with several (e. e., -3) m1. poi:-v

glucos'ide', tructoside,=etc., or.-fone R represents a drogen or] 'acyl "such as acetyl. etc.

a glycosi'de .grouptjthe-compound is'a vmonoslycoside. r

The following example: qtthe' preparation of a preferred compound or the present v entionwillserve for illustrativepurposm m d-amm-erz-manvzaa mumvaaquinone A mixture of about 3- or Z methyI-IA- naphthohydroquinone and "1.7 grams of 'p-d-glucose pentacetate with a catalyshfeig 0.15 gram oi p-toluenesulfonic acid, is 'flrs'theated and stirred at a temperature of about 1 30- 135 C. for about 30 minutes-duringwhich some acetic acid is evolved. The reaction product dissolved in 300 ml. of benzene is then washed with water, dilute alkali and again'with water and the alkaline extract acidified with dilute acid, .extracted with ether and the ether removed by evaporation. The alkali soluble residue resembling tar is small in amount and may be discarded. The benzene solution containing the alkali insoluble material is dried and the benzene removed under reduced pressure in the usual way. I The dark colored syrup remaining is then taken up in ether, decolorized with carbon and the residue after evaporation of the ether crystallized from 95 per cent ethanol. The acetylated diglucoside o1 2-methyl-1,4-naphthohydroquinone obtained melts at about 208 C.

The hydrolysis of the acetylated di-glucoside obtained, for example, by the above described process may be carried out as follows: About 250 mg. of the acetylated glucoside is first mixed am at mu g' .jethanol'. The alcohol is then.re.- I moved irom.. the extract containing the desired glucoside,ahd 'thehresidue ,.crystallized fromtthe water The z-methyl L i-naphthohy v dro( '1'1inane' di p'd g lucoside obtained has been found to I have -ran. antlhemorrhagic: ativity as Where both R-s arealy'co'eide groups we com- 9 high; as 5 00 per mg. when injected as an aqueous solution.

- Ia 'e--a l exam Ie ,the process. described therein.v is; merely illustrative and the present in. .ventionis hot-limited 'the're'to. otherzmethods for the preparationoi 'glycosides orv various modl. 'flcations thereof may be employed if. desired in the preparation oi the' haphthohy'drbquinone .glycosides otthe present invention.

- It will be understood that the present invention is not'limited to the p-d-glycosides or the above example. The 5-1 as well as the 11-11 and a-l glycosides or mixtures of the same may be prepared by selecting the proper form or sugar.

' toses. etc; as well as the disaccharides such as It will also be understood that the present inventlon is not limited to glycosides prepared from glucose. Other sugars suitable for use in the preparation '01 theglycosides of the present invention include monosaccharides, e. g., hexoses such astructose, galactose, mannose, etc., pentoses such-as arabinose, xylose, etc., and hep- 'such as glucoside and the other R represents another type of glycoside such as fructoside) may be prepared by employing a mixture of sugars selected in accordance with the type of glycoslde desired.

or e-anxrnuJ-nhrhind I maoaunvona In the above example both R's of the representative formula areglycosides and the resulting product is a di-glycoside. The monoglycoside (i. e., where one B represents a glycoside and the other R represents hydrogen) may be prepared by employing the proper ratio of sugar and naphthohydroqulnone. It the mono-glycoside derivative is prepared (it being understood that the glyco'side group may be at'the 1 -or 4 position)" it has been found desirable to protect the hydroxyl (OH)' group by replacing the hydrogen with an acyl group such as acetyl in order to form an ester or'acetate'group.

The compounds of the present invention are stable and due to water solubility are readily administered in accordance with medical practices.

Investigations indicate the 2-methyl-1,4-naphthohydroquinone-glyucosides to possess particularly high antihemorrhagic activity coupled with low toxicity when-injected in aqueous solutions.

It will be understood that the present invention is not limited to the above illustrative examples. All modifications coming within the scope of the present invention are intended to be covered by the following claims.

We claim:

1. Glycosides of 2-alkyl-1,4-naphthohydroqul- Y 35 peutic and being droquinone. said glucosides being prepared as therapeutics and being characterized by antihemorrhagic activity.

5. A compound represented by the formula:

said compound being prepared as a therapeutic and being characterized by antihemorrhagic 15 activity.

6. A compound represented by the formula in which the R's represent glucoside groups, said 25 compound being prepared as a therapeutic and being characterized by antihemorrhagic activity.

'7. A compound represented by the formula, oi! claim 6 in which the Rs represent d-glucoside groups, said compound being prepared as a thera- 3a peutic and being characterized by antihemorrhagic activity.

8. A compound represented by the formula of claim 6 in which the R's represent B-d-glucoside groups, said compound being prepared as a theracharacterized by antihemor- BRYONRIEGEL. 2mm G. sm'rn.

rhagic activity.

CERTIFICATE OF CORRECTION. Patent No. 2,356,890.; De ce1nber 11+, 9 45.

It is hereby certiiiejd that ci'roi' appears in 'theprinted specification 1 of the abqve mgnbered pateht requiring corrcction s follows: Page 1, sec.

0nd col mn, line 17;- after "rroin' strike out'9the"; and that the said Let- 't ersjPatent should be read with this co-i'rection therein that the same may corifom to the recobd 'of "the. cage in the Patent Officer Signed and se ald this 29mg of Febmary, A D. 191 1;.

: Leslie Fr a.zer

(Seal) I Acting Commissiopcr of Patents. 

